Odontology

https://doi.org/10.1007/s10266-023-00863-4

REVIEW ARTICLE

Xenogeneic collagen matrix vs. connective tissue graft

for the treatment of multiple gingival recession: a systematic review
and meta‑analysis
Lorena Zegarra‑Caceres1 · Ariana Orellano‑Merluzzi1 · Francisco Wilker Mustafa Gomes Muniz2 ·
Sérgio Luis Scombatti de Souza3 · Marcelo Faveri4 · Jonathan Meza‑Mauricio1

Received: 27 June 2023 / Accepted: 3 October 2023

© The Author(s), under exclusive licence to The Society of The Nippon Dental University 2023

Abstract
The aim of this systematic review (SR) compared the effect of xenogeneic collagen matrix (XCM) vs. connective tissue
graft (CTG) for the treatment of multiple gingival recession (MGR) Miller Class I and II or Cairo type I. Five databases
were searched up to August 2022 for randomized clinical trials (RCTs) comparing the clinical effects of XCM vs. CTG in
the treatment of MGR. The random effects model of mean differences was used to determine reduction of gingival recession
(GR), gain in keratinized tissue width (KTW), gain in gingival thickness (GT) and gain in clinical attachment level (CAL).
The risk ratio was used to complete root coverage (CRC) at 6 and 12 months. 10 RCTs, representing 1095 and 649 GR at
6 and 12 months, respectively, were included in this SR. The meta-analysis showed no statistically significant difference
in GR reduction, KTW gain GT gain or CAL gain between groups at 6 months. However, at 12 months of follow-up,
differences favoring the control group were observed (p < 0.05). CRC was significantly higher in the CTG group at 6 and
12 months. Regarding dentine hypersensitivity (DH), no statistically significant differences were found between groups at
6 and 12 months of follow-up (p < 0.05). At 12 months, CTG showed significantly superior clinical results in the treatment
of MGR: however, this difference was not observed in the decrease of DH.

Keyword Gingival recessions · Coronally advanced flap · Connective tissue graft · Acellular dermis

Background

Gingival recession (GR) is the pathological apical shift

Lorena Zegarra Caceres and Ariana Orellano Merluzzi have
contributed equally to this work.
* Jonathan Meza‑Mauricio
emezam@cientifica.edu.pe
1
School of dentistry Universidad Cientifica del Sur Lima,
Calle Cantuarias 398, Miraflores, Lima 15048, Peru
2
Department of Periodontology, Federal University of Pelotas,
Pelotas, Brazil
3
Department of Oral and Maxillofacial Surgery
and Periodontology, School of Dentistry of Ribeirão Preto,
University of São Paulo - USP, Ribeirão Preto, SP, Brazil
4 CTG is considered the “gold standard” approach in terms of
Department of Periodontology and Oral Implantology, Dental
Research Division, University of Guarulhos, Guarulhos, SP,
Brazil
of the gingival margin from its normal position leading to
exposure of the root surface [1]. GR is frequently associated
with esthetic complaints, root hypersensitivity, mechanical
root wear, cervical root caries, and difficulties to achieve
optimal plaque control [2]. Surgical procedures to treat
GR are primarily aimed at covering exposed root surfaces
and increasing the thickness and keratinized tissue width
(KTW) to improve clinical parameters and patient‐centered
outcomes [3, 4].
Nowadays, various periodontal plastic procedures have
been reported to treat GR, including coronally advanced
flaps (CAF) [5], laterally moved flaps [6] and the tunnel
technique (TUN) [7], which may or may not be accompanied
by connective tissue graft (CTG). The CAF associated with
clinical outcomes in root coverage procedures [8, 9].

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However, CTGs have limited availability especially when (PRISMA) statement [33]. The protocol for this SR was
treating multiple gingival recessions (MGR) [10]. The need registered in the International Prospective Register of
for a second surgical site can lead to increased postoperative Reviews (PROSPERO) with the number CRD 42022350757.
pain and patient discomfort [11]. There is also a greater risk of
intra- and postoperative bleeding and increased surgical time Focused question
[12, 13]. Taking all of this into account, several clinicians and
researchers have been searching for new materials to replace In the surgical treatment of patients with Miller class I and
autogenous grafts [14, 15]. II or Cairo type I MGR, what are the clinical effects of XCM
The use of xenogeneic collagen matrix (XCM) in in comparison with CTG, in terms of GR reduction, gain in
periodontal plastic surgery has received increasing attention keratinized tissue width (KTW), gain in gingival thickness
in the last decades, because it is a less invasive root coverage (GT), complete root coverage (CRC), gain in clinical
procedure [16, 17]. On the other hand, substitutes are not attachment level (CAL) and patient-related outcomes?
limited to treat gingival recessions; they are also applicable
when tissue and bone regeneration are needed simultaneously
Eligibility criteria
[18, 19]. However, periodontal tissues could hardly be
regenerate using a XCM without providing regenerative niches
The inclusion criteria were based on the PICOS strategy
with biological cues to activate the signaling pathway for the
[34]. Only studies meeting the following criteria were
whole regeneration of cementum, periodontium, and alveolar
included:
bone simultaneously [20].
Based on the principle of tissue engineering, it is reasonable
to assume that XCM may also serve as a viable scaffold for Inclusion criteria (PICOS)
the ingrowth of cells following growth factor-mediated root
coverage procedures. Recently, a clinical study showed that Population
recombinant human platelet-derived growth factor rhPDGF
enhances the clinical and aesthetic outcomes of MGR above Adult patients (≥ 18 years) with Miller class I and II
the results achieved with CAF + XCM alone [21]. [35] or Cairo type I [36] MGRs undergoing root coverage
However, XCM has been shown to promote an increase procedures. No restriction on ethnicity, gender, or root
of keratinized tissue in both the width and thickness not only coverage technique were imposed.
around natural tooth but also around dental implants [22]. A
recent review reported that XCM had better outcomes than Intervention
CAF alone in terms of root coverage [23].
XCM can also be used without limitation in terms of size, Root coverage procedure with the use of XCM.
shape and homogeneous thickness and a larger variety already
exists on the market [24, 25]. Recently, new XCMs have been Comparison
proposed with different manufacturing processes that lead to
different structural and physical characteristics, which could Root coverage procedure with the use of CTG.
have different outcomes [15, 26].
Nonetheless, there is no clear evidence on the efficacy of
Outcome
XCM for the treatment of gingival recessions. Some rand-
omized clinical studies have reported the efficacy of XCM in
GR reduction (primary outcome variable), gain in KTW,
the treatment of MGRs, showing better outcomes than CTG in
gain GT, CRC, gain in CAL and patient-related outcomes
terms of GR reduction [27–30]. However, other clinicals studies
(secondary outcomes variables) at 6 and 12 months.
have described better outcomes with CTG [24, 31, 32]. There-
fore, the aim of this systematic review (SR) was to evaluate the
efficacy of XCM vs. CTG for the treatment of MGR. Study design

Randomized clinical trials (RCT).

Methods
Exclusion criteria
Protocol and registration
i. Studies with insufficient information about the study
This SR was conducted in accordance with the Preferred design.
Reporting Items for Systematic Reviews and Meta-Analysis ii. Studies with less than 10 participants per group.

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iii. Studies that included individuals with systemic dis-
eases.
Search strategy
The MEDLINE (PubMed), Embase, Scopus, Cochrane
Library (CENTRAL) and Web of science databases were
searched up to August 2022 by two independent reviewers
(J.M.M. and F.W.M.G.M.). Complete search strategies for
the databases are presented in Appendix 1. Furthermore,
a manual search of relevant primary sources related to the
topic was made in Journal of Dental Research, Journal of
Clinical Periodontology, Journal of Periodontology, Journal
of Periodontal Research and Clinical Oral Investigations.
Finally, the references of the studies included were explored
to capture any potential additional records, as suggested by
Greenhalgh and Peacock [37].
Data collection, extraction and management
Screening and selection of papers
Two calibrated reviewers (A.A.O.M and L.A.Z.C), tested
by Cohen’s kappa test [38], independently screened titles
and abstracts for inclusion in the databases using Rayyan
Systems Inc. (https://​www.​rayyan.​ai/). After identifying
potentially relevant studies, full-text articles were obtained.
Any disagreement was solved by a discussion with a third
reviewer (J.M.M).
Search outcomes and evaluation
The studies fulfilling the eligibility criteria were processed
for data extraction conducted by two independent
researchers (A.A.O.M and L.A.Z.C), using an electronic
spreadsheet (Word, Microsoft Corporation, Washington,
USA). Disagreements were resolved by discussion with
a third reviewer (MF). In the event of missing data, a
request was sent to the authors. For each study selected,
the following variables were collected: name of author(s),
year of publication, country of publication, study design,
GR defect, number of patients/teeth, gender, age,
intervention (number of sites in each experimental group),
clinical parameters evaluated, patient reported outcomes
measures (PROMS), follow-up period and main findings
for all outcomes of interest.
Risk of bias in individual studies
Two reviewers (A.A.O.M and L.A.Z.C), assessed the
risk of bias in the studies selected, using the Cochrane
risk-of-bias tool, RoB 2 (version 2, available at: https://​
www.​r isko​fbias.​info/​welco​me/​rob-2-​0-​tool/​curre​nt-​versi​
on-​of-​rob-2). The authors of this SR decided to assess the
result related to “assignment to intervention (the intention
to treat effect)” and five domains were examined: (i) bias
arising from the process of randomization and allocation
concealment, (ii) bias due to deviations from intended
interventions that involved masking of participants and
the team of researchers, (iii) bias due to missing outcome
data, (iv) bias in the measurement of the outcome, and (v)
bias in selection of the result reported [39]. Based on the
responses to the signaling questions and algorithms of this
tool, each domain was judged to have “low risk of bias”,
“some concerns relating to the risk of bias,” or “high risk
of bias”. Studies were categorized as being at low risk of
bias (all domains were at low risk of bias), high risk of
bias (one or more domains were at high risk of bias), some
concerns (if one or more domains had some concerns)
[39]. Disagreements were resolved by discussion consult-
ing a third reviewer (SLSS).
Data synthesis and synthesis of the results
One author was responsible for statistical data collection and
analysis. Meta-analyses were performed considering the mean
difference (MD) between baseline and two different follow-ups
(6 and 12 months) for each outcome (GR, KTW, GT, CAL
and dentine hypersensitivity [DH]). Two additional meta-
analyses were performed considering the risk ratio (RR) at 6
and 12 months for CRC. Subgroup analyses were performed,
whenever possible, considering the different flaps (CAF or
TUN) and brands of XCM (Mucograft or Mucoderm). Both
subgroup analyses were performed at 6 and 12 months of
follow-up.
The RevMan software (version 5.3 for Windows) was used
to perform both meta-analyses. Heterogeneity was assessed
with the Q test and quantified by I­ 2. As the methodological
characteristics differed among the studies included, both
analyses were performed using a random-effect model.
Statistical significance was established as p < 0.05.
Certainty of the evidence
The certainty of the evidence was evaluated by the GRADE
approach [40, 41]. This evaluation was performed for each
meta-analysis considering the overall effect. The risk of bias,
inconsistency, indirectness, imprecision, and other aspects
were considered to determine the certainty of the evidence.
Independent analyses of both outcomes were performed
(GR at 6 and 12 months of follow-up), and a summary of the
findings was prepared.
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Results
Study selection
The electronic search strategy identified 2,965 titles. After
removing duplicates, 1482 records were screened on the
basis of title and abstract. Full text assessment was per-
formed for 13 articles. Among these, three studies were
excluded for not fulfilling the eligibility criteria (Appen-
dix 2) [25, 42, 43]. Therefore, 10 studies were included in
the present study (Fig. 1). The reviewers showed excellent
agreement (K = 0.89).
Fig. 1  PRISMA flow chart of manuscripts screened by the review process
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Characteristics of the studies included
The reports included were 10 RCTs (seven [27–32, 44] with
a split-mouth design and three [7, 17, 24] with a parallel
design) conducted between 2013 and 2021. The main
methodological characteristics of the studies included are
presented in Table 1. Three clinical studies were conducted
in Brazil [17, 28, 30], two in Poland [7, 32], and the others
in different countries, including Serbia [29], France [31]
Hungary [44], Germany [24] and Turkey [27].
Of all the clinical studies included in this SR, five stud-
ies used the CAF [17, 24, 27, 28, 30] and TUN [7, 29, 31,
32, 44] techniques. Data of 1,095 and 649 Miller class I
 Table 1  Characteristics and main results of the studies included
Author, Year Study design GR Defect Number of M/F Interventions (n Clinical Patient reported Follow-up Main findings
(Country) patients/teeth Age of teeth) parameters outcomes (Months)
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Aroca et al., 2013 RCT Split-mouth GR depth > 2 mm 22 patients with NR TUN + XCM GR, KTW, GT, Dentine 12 At 12 months,
(Hungary) Miller class I 156 teeth with NR (n = 78) test CRC and CAL hypersensitivity the decrease
or II GR TUN + CTG​ and esthetic of GR, KTW
Maxillary and (n = 78) control (VAS) gain and CAL
mandible gain obtained
between the test
and control group
had statistically
significant
differences in
favor of the CTG
group (p < 0.05).
The CTG
group showed
significantly
greater
improvements
of CRC
compared with
the use of XCM
(p = 0.03). All
patients reported
a decrease
in dentine
hypersensitivity.
No statistically
significant
difference
was detected
between groups
for esthetic
satisfaction
(p > 0.05)

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 Table 1  (continued)
Author, Year Study design GR Defect Number of M/F Interventions (n Clinical Patient reported Follow-up Main findings
(Country) patients/teeth Age of teeth) parameters outcomes (Months)

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Cieslik- RCT Parallel GR depth > 2 mm 28 patients with 9/19 TUN + XCM GR, KTW, CRC Postoperative pain 3 and 6 The reduction
Wegemund Miller class I 106 teeth with 20–50 (n = 59) test and CAL (VAS) of GR after
et al., 2016 or II RG TUN + CTG​ 6 months showed
(Poland) Maxillary and (n = 47) control no statistically
mandible significant
difference
between groups.
KTW gain, CAL
gain and after
6 months was
similar in both
groups (p > 0.05).
However, CRC
was significantly
higher in the
CTG group.
Patients in the test
group reported
statistically
greater pain
7 days after
surgery
Tonetti et al., RCT​ GR depth ≥ 3 mm 187 patients with 69/118 CAF + XCM GR, Postoperative 6 There were
2018 Parallel Cairo type I 485 teeth with NR (n = 242) test KTW and CRC​ pain (VAS) statistically
(Germany) Maxillary GR CAF + CTG​ and dentine significant
(n = 243) control hypersensitivity differences in GR
(VAS) reduction, KTW
gain, dentine
hypersensitivity
and CRC favoring
the CTG group
(p < 0.05).
However,
postoperative
pain was lower in
the XCM group
(p < 0.05)
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 Table 1  (continued)
Author, Year Study design GR Defect Number of M/F Interventions (n Clinical Patient reported Follow-up Main findings
(Country) patients/teeth Age of teeth) parameters outcomes (Months)
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Nahas et al., 2019 RCT Split-mouth GR depth ≥ 3 mm 15 patients with 7/8 CAF + XCM GR, KTW, CRC Postoperative 3, 6 and 12 There were no
(Brazil) Miller class I 82 teeth with 18–51 (n = 42) test and CAL pain (VAS), significant
Maxillary GR CAF + CTG​ esthetic (VAS) differences
(n = 40) control and dentine regarding GR
hypersensitivity reduction, CAL
(VAS) gain and CRC
between CTG
and XCM groups
at 12 months
(p > 0.05). The
mean KTW gain
was significantly
greater in the
CTG than the
XCM group
(p < 0.05).
Dentine
hypersensitivity
was effectively
reduced in both
groups without
significant
differences
at 12 months
(p = 0.915).
Postoperative
pain was
significantly
higher in the
CTG group
at 15 days
(p = 0.03).
Esthetic
satisfaction did
not significantly
differ between
groups at
12 months
(p > 0.05)

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 Table 1  (continued)
Author, Year Study design GR Defect Number of M/F Interventions (n Clinical Patient reported Follow-up Main findings
(Country) patients/teeth Age of teeth) parameters outcomes (Months)

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Pietruska et al., RCT Split-mouth GR depth ≥ 1 mm 20 patients with 7/13 TUN + XCM GR, KTW Not assessed 6 and 12 The reduction
2019 (Poland) Miller class I 91 teeth with 20–56 (n = 46) test GT, CRC and of GR after
and II GR TUN + CTG​ CAL 12 months was
Mandible (n = 45) control significantly
higher in the
CTG group
(p < 0.001).
CRC, GT gain,
KTW gain and
CAL gain were
significantly
higher in the
CTG than the
XCM group
(p < 0.05)
Gürlek et al., 2020 RCT Split-mouth Miller class I 12 patients with 4/8 CAF + XCM GR, KTW, CRC Not assessed 6 There were no
(Turkey) and II 82 teeth with 18–56 (n = 41) test and CAL significant
Maxillary and RG CAF + CTG​ differences
mandible (n = 41) control regarding GR
reduction, KTW
gain, and CRC
and CAL gain
between groups
at 6 months
(p > 0.05)
Rakasevic et al., RCT Split-mouth GR depth ≥ 2 mm 20 patients with 9/11 TUN + XCM GR, KTW Not assessed 6 and 12 There were no
2020 (Serbia) Cairo type I 114 teeth with 30.5 ± 7.9 (n = 62) test GT, CRC and significant
Maxillary and GR TUN + CTG CAL differences
mandible (n = 52) control regarding GR
reduction, KTW
gain, CAL gain,
and CRC between
the groups
at 12 months
(p > 0.05). The
XCM group
showed greater
gain in GT than
the CTG group
at 12 months
(p = 0.045)
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 Table 1  (continued)
Author, Year Study design GR Defect Number of M/F Interventions (n Clinical Patient reported Follow-up Main findings
(Country) patients/teeth Age of teeth) parameters outcomes (Months)
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Vincent -Bugnas RCT Split-mouth GR depth ≥ 1 mm 12 patients with 4/8 TUN + XCM GR, KTW GT, Postoperative pain 12 The CTG group
et al., 2020 Cairo type I 74 teeth with 23–55 (n = 37) test CRC and CAL (VAS) showed a
(France) Maxillary GR TUN + CTG​ significant
(n = 37) control difference
regarding GR
reduction, CAL
gain and GT gain
than the XCM
group (p < 0.05).
However, KTW
gain was similar
between groups
(p = 0.190).
Postoperative
pain was
significantly
higher in the
CTG group
(p < 0.001)
Maluta et al., RCT Split-mouth Miller class I 15 patients with 6/9 CAF + XCM GR, KTW, CRC Not assessed 6 Both groups
2021 (Brazil) and II 94 teeth with 37.47 ± 9.1 (n = 48) test and CAL obtained similar
Maxillary and GR CAF + CTG​ GR reduction,
mandible (n = 46) control KTW gain
and CAL gain
(p > 0.05).
However, the
frequency of
CRC was greater
in the CTG than
the XDM group
(p = 0.045)

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 Table 1  (continued)
Author, Year Study design GR Defect Number of M/F Interventions (n Clinical Patient reported Follow-up Main findings
(Country) patients/teeth Age of teeth) parameters outcomes (Months)

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Meza- Mauricio RCT Parallel GR depth ≥ 2 mm 42 patients with 17/24 CAF + XCM GR, KTW, GT, Postoperative 6 and 12 There were
et al., 2021 Cairo type I 130 teeth with 18–42 (n = 64) test CRC and CAL pain (VAS), significant
(Brazil) Maxillary RG CAF + CTG​ esthetic (VAS) differences
(n = 66) control and dentine regarding the
hypersensitivity reduction of GR,
(VAS), OHIP- GT gain and CRC
14 favoring the CTG
group (p < 0.05).
Both procedures
showed similar
CAL gain and
KTW gain
(p > 0.05). XDM
demonstrated
advantages
over CTG with
regard to patient
morbidity
(p < 0.05).
Both groups
improved dentine
hypersensitivity,
patient esthetic
score and
OHIP-14 without
significant
differences at
12 months

CAF coronally advanced flap; CAL clinical attachment level; CRC​ complete root coverage; CTG​ connective tissue graft; F female; GR: gingival recession; GT gingival thickness; KTW
keratinized tissue width; M male; NR not reported; OHIP-14 Oral Health Impact Profile-14; RCT​ randomized clinical trial; TUN tunnel technique; VAS visual analog scale; XCM xenogeneic
collagen matrix
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and II GR (Cairo type I) were collected and analyzed at
6- and 12-month post-treatment, respectively. Seven studies
[7, 17, 24, 27–30] performing the analysis at 6 months were
included; in the experimental group 535 teeth with GR were
analyzed and in the control group 560 teeth were analyzed.
On the other hand, six studies [17, 28, 29, 31, 32, 44] per-
formed the analysis at 12 months in 331 and 318 teeth with
GR in the test and control groups, respectively.
Risk of bias in individual studies
An adequate method of sequence generation was reported in
all the studies included in this SR. Regarding deviations from
intended interventions, 100% of the studies were classified as
having a “low “risk of bias. All studies described data out-
comes for all the participants included in the analysis. Finally,
three studies did not report a pre-specified analysis plan before
initiation of the study [27, 32, 44]. In general, only three stud-
ies were considered to have some concerns of overall risk of
bias. A summary of bias results is shown in (Fig. 2).
Clinical results
All the clinical studies included in this SR evaluated the
following clinical parameters: reduction in GR and gain in
KTW at 6 and/or 12 months of follow-up [7, 17, 24, 27–32,
44]. On comparing XCM vs. CTG at 6 months, six studies
did not find significant differences between the groups in
terms of a reduction in GR [7, 17, 27–30]. However, one
study showed significant differences for the CTG group
[24]. On the other hand, at 12 months two studies did not
find statistically significant differences between the groups
Fig. 2  Summary of risk of bias of trials included in systematic review, according to Cochrane risk-of-bias tool, RoB2. Plus, sign indicates low
risk of bias; minus sign indicates high risk of bias; question mark that indicates some concerns for the risk of bias
[28, 29], but four studies showed a significant difference for
the CTG group [17, 31, 32, 44]. In addition, two and three
studies found significant differences for the CTG group in
terms of gain in KTW at 6 [24, 28] and 12 [28, 32, 44]
months, respectively.
All the studies included evaluated CRC at 6 months;
three studies found no significant difference between
groups [27–29]. However, four studies showed significant
differences in favor of the CTG group [7, 17, 24, 30]. Of the
six studies included with data for 12 months of follow-up,
five evaluated CRC. Of these, two studies showed no
significant differences [28, 29], and three showed significant
differences for the CTG group [17, 31, 32]. In addition, only
two of the seven studies evaluated GT gain at 6 months. One
of these studies [29] found no significant differences between
groups, but the other showed significantly differences for
the CTG group [17]. On the other hand, of the six studies
evaluating CRC at 12 months, four showed significant
differences in GT gain for the CTG group [17, 31, 32, 44]
and one study for the XCM group [29]. Finally, six studies
evaluated CAL gain, with three studies showing significant
differences favoring the XCM group at 6 [17, 28, 30] and
12 months [31, 32, 44].
Patient‑related outcome measurements (PROMS)
Five studies included in this SR evaluated postoperative pain
using a visual analog scale (VAS) [7, 17, 24, 28, 31]. Three
studies showed significantly lower pain in the XCM group
than the CTG group up to seven [17, 24] and 15 [28] days
after surgery. One study evaluated the mean postoperative
pain during the first 14 days and reported that the XCM
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group produced less pain than the CTG group (p < 0.001)
[31]. However, one study showed significantly higher pain
and swelling in the XCM group compared to the CTG group
[7].
On the other hand, four studies evaluated DH [17, 24,
28, 44]. Two [17, 28] did not find significant differences
between the groups at 12 months, while one study showed
significantly lower DH in the CTG group [24]. Finally, one
study reported that DH decreased in all patients but did not
report whether there were significant differences between
the XCM and CTG groups [44].
Three studies evaluated the patient esthetic satisfaction
with a VAS and described an improvement without signifi-
cant differences between groups at 12 months (p < 0.05) [17,
28, 44]. Finally, only one study evaluated the improvement
in quality after a root coverage procedure without significant
differences between groups at 12 months [17].
Synthesis of meta‑analysis results
All the articles reported data on a reduction in GR and gain
in KTW at 6 [7, 17, 24, 27–30] and 12 months [17, 28, 29,
31, 32, 44]. All studies also evaluated CRC at 6 months [7,
17, 24, 27–30], but only five studies did so at 12 months
[17, 28, 29, 31, 32]. In addition, data on GT gain was only
reported in two studies at 6 months [17, 29] and five stud-
ies at 12 months [17, 29, 31, 32, 44]. Finally, CAL was
evaluated in six studies at 6 months [7, 17, 27–30] and
12 months [17, 28, 29, 31, 32, 44]. In this SR we also per-
formed meta-analyses of other variables, such as probing
depth (Appendix 3).
Fig. 3  Comparison of reduction in gingival recession between connective tissue graft and xenogeneic collagen matrix at 6 months (subgroup
analysis considered the different techniques of root coverage)
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Subgroup analyses were performed for all variables at 6
and 12 months according to the type of flap (CAF or TUN).
On the other hand, we also performed subgroups analyses
according to the brands of XCM (Appendix 4).
Reduction in GR
Seven studies evaluated the reduction in GR at 6 months of
follow-up, and showed no statistically significant differences
between groups (MD: 0.12; 95% confidence interval [CI]:
– 0.05−0.30), and moderate heterogeneity (I2 = 64%, p = 0.01)
(Fig. 3). Subgroups analyses were performed for studies uti-
lizing CAF or TUN techniques. For the TUN technique the
meta-analysis did not reveal a statistically significant differ-
ence between the XCM or CTG groups (p = 0.19). However,
for the CAF technique, the meta-analysis showed a statisti-
cally significant difference in GR reduction, favoring the CTG
group (MD: 0.22; 95%CI: 0.06−0.38 n = 5), with moderate
heterogeneity (I2 = 48%, p = 0.10) (Fig. 3).
At 12 months of follow-up, statistically significant dif-
ferences were detected between groups, favoring the CTG
group (MD: 0.33; 95% CI: 0.19−0.46; n = 6), and show-
ing low heterogeneity (I2 = 26%, p = 0.24) (Fig. 4). These
analyses revealed a statistically significant difference in the
reduction of GR in favor of the CTG group regardless of the
root coverage technique analyzed (Fig. 4).
Gain in KTW
Seven studies evaluated the gain in KTW at 6 months of
follow-up. The meta-analysis showed no statistically sig-
nificant differences between groups (MD: 0.28; 95%CI:
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Fig. 4  Comparison of reduction in gingival recession between connective tissue graft and xenogeneic collagen matrix at 12 months (subgroup
analysis considered the different techniques for root coverage)

0.00−0.57), presenting high heterogeneity (I 2 = 73%,
p = 0.001) (Fig. 5). Subgroup analyses were performed for
studies utilizing CAF or TUN techniques. For the TUN tech-
nique the meta-analysis did not reveal a statistically signifi-
cant difference between the groups. However, for the CAF
technique, the meta-analysis showed a statistically signifi-
cant difference in KTW gain, favoring the CTG group (MD:
0.39; 95%CI:0.09−0.68 n = 5), presenting high heterogeneity
(I2 = 73%, p = 0.006) (Fig. 5).
At 12 months of follow-up, statistically significant dif-
ferences were detected between groups, favoring the CTG
group (MD: 0.69; 95%CI: 0.11−1.27; n = 6), showing high
heterogeneity (I2 = 92%, p < 0.01) (Fig. 6). However, the
subgroup analyses did not show statistically significant dif-
ferences between the XCM and CTG groups for the TUN
technique. When the subgroup analysis was performed for
studies with only the CAF technique, a significant differ-
ence in KTW gain was observed in favor of the CTG group
(MD: 0.54; 95%CI: 0.04−1.04; n = 2), showing moderate
heterogeneity (I2 = 67%, p = 0.08) (Fig. 6).

Fig. 5  Comparison of gain in keratinized tissue width between connective tissue graft and xenogeneic collagen matrix at 6 months (subgroup
analysis considered the different techniques of root coverage)

13

Fig. 6  Comparison of gain in keratinized tissue width between connective tissue graft and xenogeneic collagen matrix at 12 months (subgroup
analysis considered the different techniques for root coverage)
Gain in GT
Figure 7 shows the forest plot including the two studies
comparing GT gain between the XCM and CTG groups at
6 months of follow-up. The meta-analysis showed no sta-
tistically significant differences between groups (MD: 0.14;
95% CI – 0.11−0.40), showing high heterogeneity (I2 = 90%,
p = 0.001). For the TUN technique the meta-analysis did not
reveal a statistically significant difference between the groups.
However, for the CAF technique the meta-analysis showed
a statistically significant difference in GT gain, favoring the
CTG group (MD: 0.27; 95 CI 0.16−0.38 n = 1).
At 12 months of follow-up, statistically significant dif-
ferences were detected between groups, favoring the CTG
Fig. 7  Comparison of gain in gingival thickness between connective tissue graft and xenogeneic collagen matrix at 6 months (subgroup analysis
considered the different techniques for root coverage)
13
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group (MD: 0.37; 95% CI 0.07−0.68; n = 5), showing high
heterogeneity (I2 = 97%, p < 0.01) (Fig. 8). The subgroup
analysis showed statistically significant differences between
the XCM and CTG groups for both techniques (Fig. 8).
CRC​
For this outcome, it was demonstrated that the CTG
groups presented 24% (RR: 1.24; 95%CI: 1.13–1.36;
n = 7) (Fig. 9) and 47% (RR: 1.47; 95%CI: 1.06–2.05;
n = 5) (Fig. 10) higher RR for CRC compared to XCM, at
6 and 12 months of follow-up, respectively. However, the
subgroup analyses did not show statistically significant
differences between the XCM and CTG groups for the
Odontology

Fig. 8  Comparison of gain in gingival thickness between connective tissue graft and xenogeneic collagen matrix at 12 months (subgroup analy-
sis considered the different techniques for root coverage)

TUN technique at either 6 or 12 months of follow-up. Gain in CAL

When the subgroups analyses were performed for studies
using only the CAF technique, a significant difference
in CRC was observed in favor of the CTG group (RR:
1.27; 95% CI 1.13−1.43; n = 5)showing low heterogeneity
(I2 = 33%, p = 0.20) at 6 months and (RR: 1.20; 95%CI:
1.01−1.42; n = 2) 12 months (I2 = 0%, p = 0.70).
Six studies evaluated the gain in CAL at 6 months of follow-
up. The meta-analysis showed no statistically significant dif-
ferences between groups (MD: 0.13; 95%CI: – 0.03−0.28),
presenting low heterogeneity (I2 = 25%, p = 0.25) (Fig. 11).
For the subgroup that used the TUN technique, the meta-
analysis did not reveal a statistically significant difference
between the XCM and CTG groups. However, for the CAF

Fig. 9  Comparison of complete root coverage between by connective tissue graft and xenogeneic collagen matrix at 6 months (subgroup analysis
considered the different techniques for root coverage)

13
 Odontology

Fig. 10  Comparison of complete root coverage between connective tissue graft and xenogeneic collagen matrix at 12 months (subgroup analysis
considered the different techniques for root coverage)

technique the meta-analysis showed a statistically signifi-
cant difference in CAL gain, favoring the CTG group (MD:
0.22; 95%CI: 0.07−0.36 n = 4), presenting no heterogeneity
(I2 = 0%, p = 0.50) (Fig. 11).
At 12 months of follow-up, statistically significant dif-
ferences were detected between groups, favoring the CTG
group (MD: 0.25; 95% CI 0.04−0.46; n = 6), showing mod-
erate heterogeneity (I2 = 51%, p = 0.07) (Fig. 12). For the
subgroup that used the TUN technique, the meta-analysis
revealed a statistically significant difference, favoring the
CTG group (MD: 0.32; 95% CI 0.08−0.57; n = 4), show-
ing moderate heterogeneity (I2 = 53%, p = 0.09) (Fig. 12).
However, when the subgroup analysis was performed for
studies with only the CAF technique the meta-analysis did
not reveal a statistically significant difference between the
XCM or CTG groups.

Fig. 11  Comparison of gain in clinical attachment level between connective tissue graft and xenogeneic collagen matrix at 6 months (subgroup
analysis considered the different techniques for root coverage)

13
Odontology

Reduction in DH Certainty of the evidence

Two studies evaluated the reduction in DH at 6 and
12 months of follow-up. The meta-analysis showed no
statistically significant differences between groups in DH
reduction (MD: 0.72; 95% CI – 0.59−2.02), presenting
moderate heterogeneity (I2 = 62%, p = 0.10) at 6 months
(Fig. 13) and (MD: 0.10; 95% CI – 0.64−0.84) presenting
no heterogeneity (I2 = 0%, p = 0.63) at 12 months (Fig. 14).
Table 2 shows the GRADE assessment for all the meta-
analyses performed in the present study. Different certainties
of the evidence were detected: high (for CRC at 6 months),
moderate (GR reduction at 12 months, CRC at 12 months,
KTW gain at 6 months, and CAL gain at 6 months), low
(GR reduction at 6 months, CAL gain at 12 months, and
DH reduction at 12 months), and very low (KTW gain at
12 months, GT gain at 6 and 12 months, PPD reduction at 6
and 12 months, and DH reduction at 6 months).

Fig. 12  Comparison of gain in clinical attachment level between connective tissue graft and xenogeneic collagen matrix at 12 months (subgroup
analysis considered the different techniques for root coverage)

Fig. 13  Comparison of reduction in dentine hypersensitivity by connective tissue graft vs. xenogeneic collagen matrix at 6 months

Fig. 14  Comparison of reduction in dentine hypersensitivity by between connective tissue graft vs xenogeneic collagen matrix at 12 months

13
 Table 2  Certainty of the evidence for each meta-analysis performed
Certainty assessment № of patients Effect Certainty Importance

13
№ of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other consid- Xenogeneic Connective Relative (95% Absolute
erations collagen tissue graft CI) (95% CI)
matrix

Gingival recession reduction at 6 months

7 randomised not serious seriousa not serious seriousb none 560 535 – MD 0.12 mm ⨁⨁◯◯ CRITICAL
trials higher Low
(0.05 lower to
0.3 higher)
Gingival recession reduction at 12 months
6 randomised seriousc not serious not serious not serious none 331 318 – MD 0.33 mm ⨁⨁⨁◯ CRITICAL
trials higher Moderate
(0.19 higher to
0.46 higher)
Complete root coverage at 6 months
7 randomised not serious not serious not serious not serious none 327/560 399/535 RR 1.24 1.790 more per ⨁⨁⨁⨁ CRITICAL
trials (58.4%) (74.6%) (1.13 to 1.36) 10.000 High
(from 970
more to 2.685
more)
Complete root coverage at 12 months
5 randomised not serious seriousd not serious not serious none 117/253 158/240 RR 1.47 3.094 more per ⨁⨁⨁◯ CRITICAL
trials (46.2%) (65.8%) (1.06 to 2.05) 10.000 Moderate
(from 395
more to 6.912
more)
Gain in keratinized tissue width at 6 months
7 randomised not serious seriousd not serious not serious none 560 535 – MD 0.28 mm ⨁⨁⨁◯ IMPORTANT
trials higher Moderate
(0 to 0.57
higher)
Gain in keratinized tissue width at 12 months
6 randomised seriouse very ­seriousf not serious not serious none 331 318 – MD 0.69 mm ⨁◯◯◯ IMPORTANT
trials higher Very low
(0.11 higher to
0.27 higher)
Gingival thickness gain at 6 months
2 randomised not serious very ­seriousg not serious very ­serioush none 128 118 – MD 0.14 mm ⨁◯◯◯ IMPORTANT
trials higher Very low
(0.11 lower to
0.4 higher)
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 Table 2  (continued)
Certainty assessment № of patients Effect Certainty Importance
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№ of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other consid- Xenogeneic Connective Relative (95% Absolute
erations collagen tissue graft CI) (95% CI)
matrix

Gingival thickness gain at 12 months

5 randomised seriousi very ­seriousj not serious not serious none 289 278 – MD 0.37 mm ⨁◯◯◯ IMPORTANT
trials higher Very low
(0.07 higher
to 0.68
higher)
Clinical attachment level gain at 6 months
6 randomised not serious not serious not serious seriousb none 318 292 – MD 0.13 mm ⨁⨁⨁◯ IMPORTANT
trials higher Moderate
(0.03 lower to
0.28 higher)
Clinical attachment level gain at 12 months
6 randomised seriousk seriousl not serious not serious none 331 318 – MD 0.25 mm ⨁⨁◯◯ IMPORTANT
trials higher Low
(0.04 higher
to 0.46
higher)
Probing depth reduction at 6 months
6 randomised not serious very ­seriousm not serious seriousb none 501 488 – MD 0.04 mm ⨁◯◯◯ IMPORTANT
trials higher Very low
(0.10 lower to
0.17 higher)
Probing depth reduction at 12 months
6 randomised seriousn very ­seriouso not serious seriousb none 331 318 – MD 0.08 mm ⨁◯◯◯ IMPORTANT
trials higher Very low
(0.10 lower to
0.27 higher)
Dentine hypersensitivity reduction at 6 months
2 randomised not serious seriousp not serious very ­serioush none 108 106 – MD 0.72 ⨁◯◯◯ IMPORTANT
trials points Very low
higher
(0.59 lower to
2.02 higher)

13
 Table 2  (continued)
Certainty assessment № of patients Effect Certainty Importance

13
№ of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other consid- Xenogeneic Connective Relative (95% Absolute
erations collagen tissue graft CI) (95% CI)
matrix

Dentine hypersensitivity reduction at 12 months

2 randomised not serious not serious not serious very ­serioush none 108 106 – MD 0.10 ⨁⨁◯◯ IMPORTANT
trials points Low
higher
(0.64 lower to
0.84 higher)

CI confidence interval; MD mean difference; RR risk ratio

a
Moderate heterogeneity was detected (I2 = 64%)
b
No statistically significant difference between groups was detected
c
Studies with some concerns regarding risk of bias weighted 51% in this analysis
d
Moderate heterogeneity was detected (I2 = 73%)
e
Studies with some concerns regarding risk of bias weighted 34.3% in this analysis
f
High heterogeneity was detected (­ I2 = 92%)
g
High heterogeneity was detected (­ I2 = 90%)
h
A very few number of participants were included and a no statically significant differences between groups was detected
i
Studies with some concerns regarding risk of bias weighted 39.8% in this analysis
j
High heterogeneity was detected (­ I2 = 97%)
k
Studies with some concerns regarding risk of bias weighted 46.2% in this analysis
l
Moderate heterogeneity was detected ­(I2 = 51%)
m
High heterogeneity was detected (­ I2 = 78%)
n
Studies with some concerns regarding risk of bias weighted 34.6% in this analysis
o
High heterogeneity was detected (­ I2 = 85%)
p
Moderate heterogeneity was detected ­(I2 = 62%)
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Odontology
Discussion
The purpose of this SR was to evaluate the effects of XCM
vs. CTG for the treatment of MGR Miller Class I and II
or Cairo type I. Our meta-analyses showed no statistically
significant differences in GR reduction, KTW gain, GT
gain, or CAL gain between groups at 6 months. However,
at 12 months of follow-up, differences were found favoring
the control group (p < 0.05).
This SR did not show statistically significant
differences between groups in terms of a reduction in
GR at 6 months. This result is not in concordance with
a recent SR which concluded that CTG was better than
XCM (SMD =  − 0.442, t =  − 2.402, p = 0.017) [45]. An
explanation for this result could that the meta-analysis
in the above mentioned included only four RCTs with
different follow-up times and different flap techniques
(CAF and TUN) [45]. In our study, subgroup analysis was
performed according to the type of flap (CAF and TUN),
and the meta-analysis showed a statistically significant
difference in GR reduction, favoring the CAF technique.
This is in accordance with a recent SR which noted that
the CAF technique appears to be associated with a higher
percentage of root coverage than the TUN technique [46].
On the other hand, another recent SR found no
significant differences in root coverage between the CTG
and XCM groups at 12 months [47]. This result is not in
agreement with our SR, and could be explained in that
this study included only two studies with localized GR,
while our SR only selected studies with MGR. A possible
explanation may be due to the less challenging nature of
gaining flap mobility with larger flaps, as is the case with
treating multiple vs. single GR. The greater extension
of the flap in MGRs facilitates passive displacement
and suturing at a coronal position [46]. Therefore,
interpretation of localized GR should be not extrapolated
to MGR, highlighting the novelty of the present study.
Some studies have suggested that KTW and GT can
influence the final surgical results and/or the long-term level
of the gingival margin after the root coverage procedure [48,
49]. In fact, this may explain the relatively high incidence
of GR relapse observed in studies that employed only CAF
for the treatment of GR [50, 51]. Thus, the combined use
of grafting materials to achieve phenotype modification
may improve not only early root coverage outcomes but
also long-term results and the maintenance of the gingival
margin over time [52]. In our meta-analysis, the CTG group
showed a higher KTW and GT gain than the XCM group
at 12 months. Up to now, CTG is still considered the gold
standard procedure in the treatment of GR because of its
superiority in clinical outcomes (including root coverage,
KTW, GT, CRC and long-term stability) [53].
CRC is an important professional outcome of periodontal
plastic surgery, and in our SR CRC was found to be
significantly higher in the CTG than the XCM group. This
result is in line with another SRs [23, 45]. A clinical study
performed a logistic regression analysis to predict the
variables that interfered in CRC after periodontal plastic
surgery [30]. The authors found no correlation between the
probability of CRC and KTW in the CTG group. On the
other hand, with XCM, the higher the KTW the greater the
CRC, with XCM presenting a similar probability of reaching
a KTW threshold of 2 mm as CTG. None of the GR with less
than 1 mm of KTW in the XDM group achieved CRC [30].
CTG is considered the “gold standard” approach in terms
of clinical outcomes in root coverage procedures. However,
the need for a second surgical site can lead to increased
postoperative pain and increased patient discomfort [11].
It has been suggested that patient-reported outcomes are
important components of a successful GR treatment [17,
54]. The aim for clinicians should not only be the final CRC
outcome, but should also satisfy patient’s concerns about
esthetics and morbidity, since patient perception of the root
coverage procedure may differ from that of professionals
[55, 56].
The present SR included five studies that evaluated
postoperative pain, with four showing significantly lower
pain in the XCM group than the CTG group [17, 24, 28, 31].
This result is in concordance with a recent network meta-
analysis that showed that the use of flap + CTG presented
statistically higher patient morbidity than flap without
gingival graft [57]. However, one study included in our SR
showed significantly higher pain in the XCM group than
the CTG group [7]. This latter study [7] used a hemostatic
collagen sponge on the palatal wound (donor site), while
the other studies did not [17, 24, 28, 31]. The hemostatic
collagen sponge has shown numerous advantages, providing
mechanical protection and establishing a matrix for clot
formation and organization [58, 59]. In addition, the use of
a collagen sponge decreases the time to achieve hemostasis
of the palatal wound [58] and produces early healing of
connective tissue graft donor sites [60].
The main indication for root-coverage procedures is
the esthetic demand of the patient [61]. In our SR, three
studies evaluated the patient esthetic satisfaction with a
VAS, demonstrating an improvement without significant
differences between groups at 12 months (p < 0.05). To
our knowledge, two network meta-analyses have evaluated
patient esthetic satisfaction [57, 62]. However, in these
studies the authors did not compare CTG with XCM. We
suggest future studies should investigate this parameter with
the same scale and follow-up time.
Our meta-analysis did not show significant differences
between the groups in reducing DH at 6 and 12 months. It
was previously believed that recovery from DH can only be
13

achieved by CRC [63]. However, several studies included
in this meta-analysis, as well as clinical experience,
demonstrate that it was possible to achieve suppression of
DH with partial root coverage [17, 24, 28, 44]. Therefore,
other mechanisms could provide complementary action to
root coverage procedures, such as natural pulpal defense
mechanisms (pulpal calcification, formation of secondary
dentin, and sclerosis) [64].
The present SR has some limitations that should be
taken into consideration. Three articles included showed
a moderate (“some concerns”) risk of bias. In addition,
blinding of participants may be impossible due to the
nature of the intervention, which required another
surgical site to obtain an autogenous soft tissue graft or
the application of XCM. Another limitation could be the
few RCTs that evaluated PROMs in the treatment of GR.
Some observations on the applicability of the results
obtained can be formulated. The application of XCM
seems to provide additional benefits in terms of a reduction
in GR when applied together with CAF. However, CTG
is still considered the gold standard procedure in the
treatment of GR. XCM seems to show similar results
to those of CTG in reducing DH. More well-designed
randomized clinical trials are needed to confirm this result.
The present SR endeavored to summarize the best,
although not always the least biased, evidence available.
The limitations of evidence were comprehensively summa-
rized in a transparent manner using the GRADE approach,
according to the most recent recommendations stated in the
Cochrane and non-Cochrane SRs [65]. Further studies are
warranted to increase the body of evidence accumulated,
considering the above-mentioned limitations.
Conclusion
Within the limitations of this study, CTG showed
significantly superior clinical results in the treatment of
MGR at 12 months. However, this difference was not
observed in the decrease of DH.
Supplementary Information The online version contains supplemen-
tary material available at https://d​ oi.o​ rg/1​ 0.1​ 007/s​ 10266-0​ 23-0​ 0863-4.
Author contribution JMM, MF conception. LZC, AOM; FWMGM,
SLSS, MF, and JMM design of the manuscript; critically review for
relevant intellectual content, writing—review and editing, and final
approval of the version to published. LZC and AOM prepared figures.
All authors reviewed the manuscript.
Funding This study was financed in part by the Coordenação de
Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—
Finance Code 001. All other funding was self-supported by the authors’
institutions.
Data availability Data will be available upon request from the cor-
responding author.
13
Odontology
Declarations
Conflict of interest The authors declare no competing interests. In-
formed consent Formal consent is not required for this type of study.
Ethical approval This article does not contain any studies conducted
with human participants or animals by any of the authors.
Informed consent Formal consent is not required for this type of study.
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